This proposal is to request support for a Keystone Symposia meeting entitled "Extrinsic Control of Tumor Genesis and Progression", organized by Thea D. Tlsty and Mary J.C. Hendrix, which will be held in Vancouver, British Columbia from March 15 - 20, 2009. It has long been known that the interactions between cells and their respective microenvironments are instructive and necessary in proper development. Cell-environment interactions play complex roles in organ homeostasis and, when altered, disease. Increasing evidence now suggests that the microenvironment also modulates critical aspects of the genesis and progression of tumors. For example, initiation, progression and even control of metastasis and latency are governed by these interactions. This modulation is most likely brought about through both genetic and epigenetic mechanisms. Currently, the signaling pathways and mechanisms of regulation are mostly unknown. This conference will bring together leaders in this field to discuss current problems and strategize on the clinical application of new insights. Public health Relevance: Current therapies for cancer are often thwarted by the genetic instability manifested by the tumor cells resulting in acquired drug resistance and metastatic abilities. The great promise in studying the controls provided by the microenvironment emerges from the stability of the surrounding stromal cells - cells which make up the support structure of biological tissues - and the hope that they can be altered without the problems of genetic instability. This symposium is designed to integrate information about tumor microenvironment with current knowledge in development, wounding, disease and therapy.